All three projects rely on genetically modified mice and the production of purified proteins and polyclonal and monoclonal antibodies. Accordingly, all three projects will be supported by the Mouse Model and Protein Expression Core (Core A), led by Dr. Loren Fong. Dr. Fong is an expert in a wide variety of practical techniques in cellular and molecular biology, including growing and manipulating mouse embryonic stem cells and the use of mouse models in biomedical research. This expertise has paid huge dividends for this PPG. Dr. Fong, working with Drs. Reue, Young, and Tontonoz, has generated conventional and tissue- specific Lipin2, Lipin3, Idol, and Tle3 knockout mice. In addition, the Core houses and genotypes mice, backcrosses mice onto inbred strains, maintains animal protocols, and organizes histological studies on mouse models. The Core also produces purified proteins for biochemical studies and for generating polyclonal and monoclonal antibodies; this has been an essential function, since our PPG has focused on newly discovered molecules, for which few reagents exist. During the prior funding period, Drs. Bensadoun, Fong and Young produced multiple antibody reagents for this PPG. Their expertise and experience will be a boon for the new antibody projects proposed in this application. Aside from antibody reagents, the Core will also produce purified recombinant proteins for biochemical and structural biology studies. All three projects of the PPG will use Core A. RELEVANCE (See instructions): This Program Project Grant proposes to define the molecular mechanisms that regulate lipid metabolism and adiposity-two events that play centrol roles in the pathogenesis of metablic disesase (e.g., obeisity and atherosclerosis). The Mouse Model and Protein Expression Core will support the PPG's goals by providing new mouse models, antibodies, and recombinant proteins to all three projects.